1. Field of the Invention
This invention relates to enteric-coated proliposomal formulations for oral medicaments. In particular, it relates to enteric-coated proliposomal formulations for poorly water soluble drugs.
2. Description of the Related Art
Among the various routes of drug administration, the oral route is preferred because of its versatility, safety and patient comfort. The encapsulation of pharmaceuticals in liposomes is useful in reducing toxicity and improving the therapeutic effectiveness of certain drugs. For example, compounds such as insulin, factor VIII, tryptophan, phenylalanine, heparin, vitamin K etc., have been investigated for their effectiveness orally, after encapsulation into liposomes. Although they represent an improvement over the prior art, oral liposome formulations have been criticized because of their instability, leakage and potential destruction in gastric fluids.
The use of proliposomes represents an alternative to conventional liposomal formulations. Proliposomes are dry, free-flowing granular products, which, upon the addition of water, disperse to form a multilamellar liposomal suspension. The stability problems associated with conventional liposomes, including aggregation, susceptibility to hydrolysis and oxidation, may be avoided by using proliposomes. The use of proliposomes is well known in the pharmaceutical field.
Although the oral ingestion of drugs represents a safe and versatile method of pharmaceutical delivery, the therapeutic efficacy of many drugs is reduced because many pharmaceuticals are labile or inactivated under the acidic conditions of the stomach. Enteric coating materials have been applied to address this deficiency. Enteric coating materials are those that ensure that acid-labile drugs remain active in the stomach upon oral ingestion such that the active ingredient is released and absorbed in the intestine. Enteric coatings materials are well known in the pharmaceutical art and include alginates, alkali-soluble acrylic resins, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and the like.
Although the use of proliposomes and the use of enteric coatings are independently known in the art, the combination of an enteric coating with a proliposomal formulation has not been disclosed. Surprisingly, when an enteric coating of the current invention is combined with a proliposomal formulation of the current invention, drug delivery is enhanced. In many embodiments of the present invent, this novel and unexpected enhancement, which results from the unique combination of an enteric coating and a proliposomal formulation, relates to increased drug absorption, stability and bioavailablity.
In many embodiments of the current invention, the combination of an enteric coating and a proliposomal formulation overcomes the disadvantages of drug delivery systems known in the prior art. For example, the utility of previous systems for orally administering labile pharmacological substances has been limited by the need to use toxic amounts of delivery agents, the instability of the systems, the inability to protect the active ingredient, the inability to effectively deliver drugs that are poorly water soluble or labile, the inadequate shelf life of the systems, the failure of the drug delivery systems to promote absorption of the active agent and the difficulties inherent to manufacturing the systems.
The current invention relates to a drug delivery system comprising at least one pharmaceutically active agent, at least one phospholipid and an enteric coating material. A particular advantage of the current invention is that it provides a simple and inexpensive system to facilitate the oral administration of medicaments. In many embodiments, this drug delivery system enhances the stability and bioavailability of pharmaceutically active agents.
In one aspect of the invention, the pharmaceutically active agent is a poorly water soluble drug.
In another aspect of the invention, the phospholipid is distearoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine or dimyristoyl phosphatidylcholine and the enteric coating material is cellulose acetate phthalate.
In another aspect of the invention, a pharmaceutical formulation is delivered in a tablet, capsule, suspension and/or liquid form. In alternative embodiments, carriers, diluents and/or lubricants are also included in the pharmaceutical formulation.
Another aspect of the invention relates to a method for making the drug delivery system comprising combining at least one pharmaceutically active agent with at least one phospholipid, and thereafter coating the combination with an enteric coating material. In alternate embodiments, pharmaceutically inactive agents, such as carriers, diluents and lubricants, are also included in the drug delivery system. Placebo may also be delivered according to certain embodiments of the invention.
A further aspect of the invention relates to a method for delivering a pharmaceutical formulation to a mammal by orally administering the formulation to the mammal. In specific embodiments, the current invention relates to preventing, diagnosing or treating an illness in a mammal with the drug delivery system of the present invention.